NEPHROLITHIASISEtiology, stone composition, medical management, and prevention

Urology Division, Surgery DepartmentMedical Faculty, University of Sumatera Utara

Epidemiology

Prevalence 2-3%, maybe in mountainous, desert & tropical areas

: = 3 : 1, peak age onset 20-40 yrs 25% stone formers have a family history Uric acid and Ca stones more frequent in,

infectious stones more common in The most common kinds of stones are

calcium oxalate, uric acid, struvite and cysteine

Composition of renal stones

Calcium oxalate 36 – 70% Calcium phosphate (hydroxyapatite) 6 – 20% Mixed Ca oxalate & Ca phosphate 11 – 31% Mg ammonium phosphate (struvite) 6 – 20% Uric acid 6 – 17% Cystine 0.5 – 3% Miscellaneous (xanthine, silicates & drug

metabolites) 1 – 4%

Factors influencing stone formation

Genetics 1. Idiopathic hypercalciuria 2. Cystinuria 3. Primary hyperoxaluria, type 1 & 2 4. Lesch-Nyhan syndrome is an X-linked disease causing hyperuricemia (def hypoxanthine- guanine fosforibosiltransferase) 5. Familial renal tubular acidosis , Ehlres-Danlos syndrome, Marfan’s syndrome, Wilson’s

disease

Environmental 1. Dietary factors - >> protein & sodium intake risk Ca stone - >> purine diets urine pH

hyperuricosuria - B6 deficiency formation & excretion

oxalate - dehydration, inadequate fluid intake, vit C

excess, Ca supplements, Ca-containing antacids

2. Geographical factors - higher during summer months - higher in southeast United States

and lower in Mid-Atlantic and Northwest

regions

Stone formation

Crystallization - stone salts that precipitate out of urine - the point of saturation of a salt in solution is called

the solubility product (Ksp) - when the product of the components of a salt (e.g. calcium and oxalate) exceeds Ksp, salt crystals will precipitate out of solution - crystallization is based on Ksp, pH, and the presence

of stone inhibitors and promoters

Nucleation - is the process by which stones form around a core, or nucleus - homogeneous stone nuclei form in solution - heterogeneous stone nuclei form around existing structures, such as cellular debris Aggregation - crystals join together to form larger clumps

TYPES OF STONE

CALCIUM OXALATE Recommended treatment : - absorptive : Ca restriction, sodium

cellulose phosphate, thiazides, fluid intake - other types : thiazide & fluid intake

URIC ACID STONES

5-10% of all stone Urine pH < 5.5 Associated with uric acid in urine, not

necessarily associated with hyperuricemia Secondary causes : gout (20%), chemoth/ for

myeloproliferative cancer Most common radioluscent

Th/ : dissolve : - fluids, alkali (citrate th/), allopurinol, protein

restriction - aim urine output > 2500 ml/day - potassium citrate or sodium bicarbonate achieve urine pH 6.5-7.0 avoid pH >7.0 can precipitate ca phosphate - if hyperuricemic or hyperuricosuric allupurinol

STRUVITE STONES

Composed of Mg ammonium phosphate crystals

= infection stones or triple phosphate stone Staghorn calculi are typically struvite stone Caused by infection with urease-producing

bacteria : - proteus id the most common - urease hydrolized urea to form ammonia alkalinizes the urine, pH and allows crystals to

form

Urine pH will be >7.2 Th/ : - surgery - AB to prevent infection / stone

recurrence - irrigation with acidic solution successful but requires lengthy,

complicated treatment and costs danger : risk of sepsis, hypermagnesemia - acetohydroxamic acid : inhibit urease; 20-70% severe side effect

CYSTINE STONES

1% of all stones Congenital disorders, autosomal recessive Caused by a defect in cystine reabsorption

in the proximal tubule Cystine poorly soluble at normal pH (pKa

8.3) Crystal form benzene ring on

microscopy

Th/ : - low methionine / sodium diet - hydrate to 3 L urine output/day - alkalinize urine : potassium citrate complex cystine - ESWL not effective

CALCIUM PHOSPHATE STONE

- urine pH > 5.5 - hypocitraturia - 70% of adults with type 1 RTA have

stones - 80% are women - associated with renal cyst

Inhibitors of CaPO4 crystallization : - Mg - pyrophosphate - citrate - nephrocalcin Th / : - potassium bicarbonate or potassium citrate correct acidosis & urine citrate - fluids - thiazides if hypercalciuric

OTHER STONES

Dihydroxyadenine radioluscent Xanthine radioluscent Matrix radioluscent Ammonium acid urate Triamterene Indinavir radioluscent

MEDICAL MANAGEMENT

DIETARY PREVENTION - fluids : urine output stone formation if possible maintain >2.5 L urine/day - coffee, tea, beer, wine stone risk - lemon juice urinary citrate risk - grapefruit juice risk

PROTEIN - dietary protein urine Ca/uric acid/oxalate & urine citrate low/moderate protein intake is desirable

CALCIURIA - except in case of absorptive hypercalciuria, Ca intake stone risk Ca binds intestinal oxalate prevent its

absorption - unless absorptive hypercalciuria maintain adequate calcium intake

SODIUM - dietary sodium urinary sodium has not been proven to stone risk sodium in moderation

ASCORBIC ACID (VITAMIN C) - metabolized to oxalate - vit C intake urinary oxalate - advice : vitamin C in moderation

OXALATE - tea, instant coffee, spinach, chocolate, nuts

oxalate (+) increase urinary oxalate - high-oxalate foods in moderation for Ca oxalate

stone former

PHARMACOLOGICAL PREVENTION

THIAZIDES - HCTZ 25-50 mg or chlorthalidone 12.5-25 mg (up to 100mg) - start with small dose, titrate as needed

CITRATE - Inhibits Ca oxalate crystallization - effective for hypocitraturic stone disease - potassium citrate 10-20 mEq w/meals - side effects : GI intolerance

ALLOPURINOL - inhibits xanthine oxidase & uric acid prod - use in uric acid & hyperuricosuric Ca oxalate

stone - 300 mg/o, max 800 mg - dose in renal failure

PHOSPHATE (ORTHOPHSOPHATE) - vit D level urinary Ca excretion - urine pyrophosphate & citrate - clinical benefits are uncertain

MAGNESIUM - urinary citrate - clinical benefits uncertain

SODIUM CELLULOSE PHOSPHATE - binds Ca in the gut and inhibits absorption - indicated for use in absorptive hypercalciuria - 5 g with meals

ANTIBIOTICS - long-term prophylaxis for struvite stone after surgical treatment - drug should be culture specific

SUMMARY

The most common type is calcium oxalate. Uric acid stones form at pH <5.5. Primary

treatment and prevention is to alkalinize the urine; surgery is also an option

Struvite stone are composed of magnesium ammonium phosphate crystals. They are classically caused by infection with a urease-producing bacterium. Urinary pH is >7.2. treatment is surgery & antibiotics

Cystine stones caused by a congenital autosomal recessive disorder.

Treatment : urinary alkalinization Calcium phosphate stones associated

with type 1 RTA Dietary interventions to prevent stones

include fluid intake, protein intake and sodium intake

Pharmacological interventions to prevent stones include thiazides, citrate, allopurinol, sodium cellulose phosphate

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